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Drink, Binge and the Genetic Link

Ever since the discovery of the DNA by Watson and Crick the imperious role of the genes in influencing an individuals physiology has been widely acknowledged. Genes produce an array of proteins, which may exert a direct effect on an individuals functioning or, may coerce other genes to perform their roles effectively. Unprecedented advances in technology have ensured that adequate research is carried out to understand the underlying causes of all complex biological issues, including alcoholism. Unfolding the pattern of inheritance is the primary step towards understanding them.

Alcoholism is the compulsive consumption of alcoholic beverages. This dependence on alcohol cannot lay claim to a single cause and is believed to vary with social, emotional and hereditary factors. 50% of the total risk for alcoholism is attributed to heritable factors. More than a dozen genes have been identified which increases a persons risk of alcoholism, rendering the condition genetically complex. Although genes are implicated in alcoholism, they never act solo. Almost all genes act in tandem with specific environment such as abuse or neglect. Poor judgments and choices are also held responsible for alcohol dependence.

Individuals who meet the criteria for dependence have several cases of alcoholism in their families. It has now been widely acknowledged that some families possess a predisposition to alcohol dependence. Variants of several genes alter an individuals vulnerability to alcohol and also influences associated habits such as addiction, problem behavior, anxiety or depression.

It was observed with perplexity that persons who were of East Asian origin became flushed on consuming alcohol. This was attributed to an elevated level of aldehyde, a metabolite of alcohol. Aldehyde imparted an unusual color and warmth to the skin, besides causing palpitations and general weakness. The enzyme res ponsible for alcohol metabolism was Aldehyde Dehydrogenase and ALDH1 was discovered to be the underlying gene. A slow metabolizing gene variant of ALDH1, which was common in South East Asian populations, caused the aldehyde build up in these individuals, ensuring a 6-fold decreased risk for alcoholism.

Alcohol dehydrogenase is another enzyme that takes an active part in alcohol metabolism. The variants of the ADH genes enhance the risk of alcoholism. It is also associated with early and heavy drinking, and alcohol-related problems.

Various research groups have documented links between the different chromosomal regions and risk for alcohol dependence. For instance, variants of the gene that codes for GABA receptors on the cell surface increases risk to alcoholism. GABA is a common inhibitory neurotransmitter in the mammalian nervous system. Research is underway to find out the underlying mechanism. It has been observed that there is a loss of inhibition in those with the variant genes, and this has lead to some of them externalizing their behavioral problem. Individuals with variants of this gene have demonstrated conduct problems and usually get into trouble with the law. Another neurotransmitter that is evaluated is acetylcholine. The variants of the genes that encode acetylcholine receptors, such as CHRM2 are known to play a role in influencing alcoholism and depression, thereby prompting individuals with these variants to internalize their problem.

Examining certain endophenotypes has helped to establish familial alcohol-dependence. Although a physical trait, endophenotypes are not visible but can be measured and they help to reveal the biological basis of a disorder. The electrical activity of the brain is one such endophenotype, which can be evaluated using electroenc ephalography (EEG). The electrophysiological pattern is heritable and tends to differ markedly between the alcoholics and the non-alcoholics. The characteristic patterns that emerge help a person to predict his alcohol dependence and mode of behavior. These patterns, therefore, are established markers of familial alcohol-dependence.

Genetic profiling through technologies like microarrays, also known as gene chips, is in increasing demand. Attempts are being made to shape treatment protocols by studying the causative genetic variants. Prevention and treatment of smoking and other abusive substances can also be improvised. This will also help the affected individuals to make informed choices based on recommendations. Although these findings are part of the inevitable evolution of the developed and developing nations the world over, it must be noted that these discoveries must not be used to stigmatize the susceptible and great care must be exercised to implement it in a socially responsible way for the collective good of mankind.


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